Transition Metal Complexes as Drugs and Chemotherapeutic Agents

When this book was first conceived as a project the expanding interest in the clinical use of platinum and gold complexes made a survey of the relevant biological properties of metal complexes timely and appropriate. This timeliness has not diminished during the gestation and final publica tion of the manuscript. The introduction contains an explanation of the layout and approach to the book, which I wrote as an overall survey of the wide variety of biological properties of metal complexes. Hopefully, the reader will see the parallels in mechanisms and behavior, even in different organisms. The writing was considerably helped by the enthusiasm and confidence (totally unearned on my part) in the project of Professor Brian James and lowe him my special thanks. I also owe a great debt of gratitude to my colleagues, and especially to Eucler Paniago, of the Universidade Federal de Minas Gerais, for their comprehension and for the initial leave of absence which allowed me to begin the project. To those who read some or all of the manuscript and made suggestions, Bernhard Lippert, Kirsten Skov, and Tom Tritton, as well as the editor's reviewer I am also grateful. As usual, the final responsibility for errors or otherwise rests with the author.

Zusammenfassung
`The book is well written, thoroughly documented and presents useful information to both scientists and clinicians.'
Oncology, 48:2
`The book is very readable, well referenced and there is a useful glossary for those baffled by pharmacological terms. The discovery of truly novel drugs in the future may well hinge on the application of the principles in inorganic chemistry - both metals and non-metals - to pharmacology. This book should therefore be welcome on all library shelves.'
Chemistry in Britain, 1990

Inhalt
Metals in Medicine.- Chemotherapeutic Agents and Drugs.- Mechanisms of Toxicity.- Metal Accumulation and Activation.- Biochemical Targets for Metal Complexes.- Summary.- References.- 1. Interaction of Metal Complexes with DNA.- 1.1. DNA and Conformation.- 1.2. Experimental Methods for the Study of Conformational Changes.- 1.3. Binding of Metal Complexes to DNA.- 1.4. Summary.- References.- 2. PlatinumAmine Complexes as Anticancer Agents.- 2.1. The Discovery of Cisplatin as an Antitumour Agent.- 2.2. Clinical Properties of Cisplatin.- 2.3. Development of Cisplatin Analogues.- 2.4. Biochemical Mechanism of Action of Platinum Complexes.- 2.5. Summary.- References.- 3. StructureActivity Relationships of Platinum Amine Complexes.- 3.1. The Requirement for Neutrality.- 3.2. Complexes of Pt(IV).- 3.3. Nature of the Leaving Group.- 3.4. Nature of the Nonleaving Group.- 3.5. Novel and Targeted Approaches to [PtX2(am)2] Complexes.- 3.6. Quantitative StructureActivity Relationships.- 3.7. Chemistry of PlatinumAmine Complexes.- 3.8. Summary.- References.- 4. Interactions of Platinum Complexes with DNA Components.- 4.1. Structural Aspects of MetalNucleobase Binding.- 4.2. Reactivity of Platinum MetalBase Complexes.- 4.3. Solid State Structural Studies.- 4.4. Structural Studies on Di- and Oligonucleotide Complexes.- 4.5. Platinum Adducts from DNA Degradation.- 4.6. On the Molecular Mechanism of Antitumour Action of Cisplatin.- 4.7. Summary.- References.- 5. The PlatinumPyrimidine Blues.- 5.1. Properties of the PlatinumPyrimidine Blues.- 5.2. Platinum Blues not Derived from Pyrimidines.- 5.3. X-Ray Structure of PlatinumPyrimidine and ?-Pyridone Blues.- 5.4. Formation of PlatinumPyrimidine and ?-Pyridone Blues.- 5.5. Studies of Crystalline Blues.-5.6. Biological Studies on PlatinumPyrimidine Blue Precursors.- 5.7. Summary.- References.- 6. Antitumour Activity of Metal Complexes.- 6.1. Platinum Group Metal Complexes.- 6.2. Copper Complexes.- 6.3. Silver and Gold.- 6.4. Organometallic Complexes.- 6.5. Summary.- References.- 7. Metal-Mediated Antibiotic Action.- 7.1. Discovery and Pharmacology of Bleomycin.- 7.2. Structure of Bleomycin and Analogues.- 7.3. Metal Complexes of Bleomycin.- 7.4. Mechanism of Action of Bleomycin.- 7.5. Other Metal Binding Antibiotics.- 7.6. Summary.- References.- 8. Metals, Metal Complexes, and Radiation.- 8.1. Interaction of Radiation and Biological Tissue.- 8.2. Chemical Modification of Radiation Damage.- 8.3. Metal Complexes as Radiation Sensitizers.- 8.4. Metal Complexes and Radioprotection.- 8.5. Activation of Metal Complexes.- 8.6. Summary.- References.- 9. Antibacterial Effects of Metal Complexes.- 9.1. Mercury and Silver Salts as Antibacterial Agents.- 9.2. Antibacterial Activity of Chelating Agents and Metal Chelates.- 9.3. Antibacterial Activity of MetalAmine Complexes.- 9.4. Redox Activity and Antibacterial Activity.- 9.5. Summary.- References.- 10. Antiviral and Antiparasitic Effects of Metal Complexes.- 10.1. Antiviral Therapy.- 10.2. Chelating Agents and Metal Complexes as Antiviral Agents.- 10.3 Metal Complexes as Antiprotozoal Agents.- 10.4. Summary.- References.- 11 Metal Complexes in Arthritis.- 11.1. Gold Complexes in the Treatment of Rheumatoid Arthritis.- 11.2. Copper in Arthritis.- 11.3. Other Metals.- 11.4. Summary.- References.- 12. Miscellaneous Uses of Metal Complexes.- 12.1. Mercurial Diuretics.- 12.2. Neuromuscular Effects of Metal Complexes.- 12.3. Nitroprusside as Vasodilator.- 12.4. Summary.- References.- Names and Abbreviations.- Glossary of Termsand Definitions.- Appendix 1.- Appendix 2.- Index of Subjects.